We hypothesized that ARG might be driving the evolution to ALF, if values PI3K Inhibitor Library of ARG were lower than expected in ALF patients, suggesting a muted immune response in this setting. Methods: Serum levels of ARG-1 isotype were measured using a sandwich type ELISA employing HRP-labeled antibody in 107 HBV patients with different phenotypes: HBV-ALF (non-immunosuppressed), acute HBV with

recovery, chronic hep B (with and without flares of activity), and, as controls, 20 acetaminophen-related ALF, 10 chronic hepatitis C and 10 healthy subjects. Results: Healthy controls had median ARG of 5 ng/mL, chronic HBV and HCV ∼25-30 ng/mL (Table), while acute HBV, HBV flares and HBV-ALF median levels were 89.2, 78.4 and 69.5 ng/mL, respectively, markedly lower than APAP median level of 968 ng/mL. HBV-ALF

ARG levels were actually lower than acute or flare HBV despite comparable aminotransferase levels. Particularly low values for ARG were found in those who died of HBV-ALF (median 30.4 ng/ mL; n=5). For chronic HBV phenotypes with relatively low AST values there was poor correlation of AST with ARG (Spearman rho); only flare or APAP patients showed strong correlations (rho >0.75). Summary/Conclusions: Despite massive hepato-cyte necrosis, low ARG levels characterize HBV-ALF and, to a lesser Cobimetinib extent, acute HBV patients, supporting the postulate of ARG-driven immunomodulation in hepatitis B. A genetically mediated alteration in ARG protein might account for the low levels observed. Further understanding of the significance of ARG levels in these settings will require mechanistic or genomic studies. Median Arginase, AST Results and Correlationby Categories and Etiologies Disclosures: William M. Lee – Consulting: Eli Lilly, Novartis; Grant/Research Support: Gilead, Roche, Vertex, BI, Anadys, BMS, merck; Speaking and Teaching: Merck Background and aims: Some orthotopic liver transplantation (OLT) patients experience HBV recurrence with detectable HBV-DNA despite hepatitis B immune globulin+lamivudine

(HBIg+LAM) prophylaxis. We analyzed changes in the HBV-qua-sispecies in patients with recurrent HBV post-OLT. Methods: Twenty-nine OLT patients included in a previous study(1) to compare LAM vs. LAM+HBIg in preventing HBV recurrence AZD9291 were followed for >10 years (mean, 154.9 months [50-188]). In patients with recurrent HBV after OLT, defined as detectable HBV-DNA by real-time PCR, a region of HBV surface gene (S, codons s92-s200), including the “a” determinant, was studied by ultra-deep pyrosequencing (UDPS, GS-Junior, Roche). Results: Twelve (41%) of 29 patients had detectable HBV-DNA at some timepoint after OLT. In addition, 4 of them were HBsAg positive. Among patients with recurrent HBV, one with, and three without HBsAg had available pre- and post-OLT samples with HBV-DNA above 10E3 IU/mL and were selected for UDPS analysis (table).